Three major therapies for cancer treatment may include surgical therapy, chemical therapy and radiation therapy. These therapies may achieve high therapeutic results, however, they may encounter with difficulties some times because the surgical therapy is invasive or they may often force to interrupt the treatment due to strong side effects caused by the therapies. It is highly desired, accordingly, to apply low-intensity pulsed ultrasound waves as applied to ultrasound diagnosis when taken cancer treatment into consideration from a non-invasive point of view. Therefore, by applying the fact that photosensitive substances such as Photofrin is activated by an acoustic cavitation phenomenon to be caused by ultrasound waves, such photosensitive substances together with low-intensity pulsed ultrasound waves have been applied particularly to non-invasive treatments of cancers (see, for example, patent literature documents Nos. 1 and 2). It is pointed out, however, that photodynamic therapy using such photosensitive substances causes the problems that the quality of life (QOL) of patients may be impaired to a great extent by application of the photosensitive substances to patients for therapy using low-intensity pulsed ultrasound waves because the patients are forced to be isolated in a dark room for such an extended period of time as long as approximately two weeks in order to prevent the patients from side effects such as cutaneous hypersensitivity caused by a light. The use of the photosensitive substances may also cause the problem with a lower activation by ultrasound waves than by a light.
Low-intensity pulsed ultrasound waves confer the merits that they can reach the deeper portion of the living body than a light can and they are highly safe to such an extent to which they are used for echo diagnosis even for embryos. They cannot be expected, however, to demonstrate effects on treatments of cancers when they are solely applied thereto. At the present time, there has proceeded the application of the low-intensity pulsed ultrasound waves in combination with nanoparticles including, for example, nanobubbles or microbubbles to gene therapy or drug delivery system (DDS) utilizing an acoustic cavitation phenomenon to be caused by the low-intensity pulsed ultrasound waves. Problems have occurred, however, with various matters including, for instance, stability of nanoparticles in the living body when applied thereto. The combined use of the low-intensity pulsed ultrasound waves with the nanoparticles is still far away from practical use.
As described above, in order to permit the low-intensity pulsed ultrasound waves to be applied to a low invasive cancer therapy, there have to be solved many problems that may include, for example, a development of an ultrasound-sensitive substance unreactive with a light and an enhancement of effects of the ultrasound waves on a local target portion of treatment.
In order to solve the problems as described above, the present inventor has investigated the action and effects of the combined use of the low-intensity pulsed ultrasound waves with an ultrasound-sensitive substance that little reacts with a light and is activated by the ultrasound waves. As a result, it has been found that, although the combined use has exhibited a remarkably favorable effects in vitro on tumor cells (a potent cellular cytotoxicity), inhibitory effects on tumor proliferation in an in vivo experiment system using animals with cancer were not recognized to such an extent as expected from the in vitro effects although they were significant (Non-patent literature document No. 3). This implies that the ultrasound-sensitive substance is not activated by the low-intensity pulsed ultrasound waves to a sufficient extent in tumor tissues.